Month: April 2007

I am going to focus on adult suicidality from Seroxat in this post. It is clear from the information in the previous posts how GSK hoodwinked the regulators for a licence to treat adults with Seroxat from 1991 onwards. They tried desperately to push for a licence to treat children with Seroxat as this would have increased its marketing profile, but they failed miserably.Also we can see from the previous links, that Seroxat clearly posed a danger to children and in the end GSK failed to prove the benefits outweighed the risks. The questions I want to ask here though are concerned with Seroxat use in the adult populations. If Seroxat greatly increases the risk of suicide, aggression and hostility in children with depression and other disorders then why wouldn’t it be the same for adults? No Doctor, psychiatrist or expert has ever been able to explain to me why the effects of Seroxat would be any different between a child or adolescent or an adult taking the drug. Why does GSK maintain that Seroxat is safe for use in the adult populations? when even they themselves admit that it can cause severe and dangerous side effects in children?

Are we to believe GSK’s original Seroxat adult clinical trial data submitted to the regulators to be an accurate and true representation of Efficacy?
Or, considering their history ,should we put our trust in an independently funded study? Well, there was an independent study done on Seroxat in August 2005. It caused a Media Storm at the time because it demonstrated that Seroxat is linked with up to a 7 fold increase in suicide compared to a placebo (sugar pill)… That means you are seven times more likely to kill yourself if you take Seroxat … And they prescribe this drug for Depression! ..
The mind boggles….

Almost 2.4 million prescriptions for the drug were issued in England last year.The data was available even before Seroxat was first licensed in 1990, the Norwegian researchers found. The findings are likely to be seized on by lawyers attempting to win damages against the drug’s manufacturer, GlaxoSmithKline, in the US and in Britain. The mental health charity Mind said the results were “extremely worrying” and confirmed what it had been arguing for years.

“By ignoring what mental health service users themselves have said about the medication and its effects, the drugs regulators may well have caused lives to be lost,” said Sophie Corlett, policy director of the charity.

Campaigners, including Mind, say the drug should be withdrawn from sale, but GSK and the Medicines and Healthcare products Regulatory Agency (MHRA) have defended it, arguing that its benefits outweighed the risks.

However the MHRA has said that too many drugs of this class, SSRIs (selective serotonin re-uptake inhibitors), have been prescribed, and has warned that they should not be given to under-18s.

The MHRA also said that an increase in suicidal thoughts among users of Seroxat “cannot be ruled out.” The new study suggests that such an increase should have been apparent from the beginning.

Sales of paroxetine have fallen sharply in the UK in the past three years after concerns about it were highlighted by the media.

A team led by Ivar Aursnes of the University of Oslo looked at 16 studies in which paroxetine had been compared with placebo, including previously unpublished data.

The trials covered a total of 190 patient-years of use of the drug and the results were published in the journal BMC Medicine.

Ms Corlett of Mind said: “This study would seem to be an extremely worrying addition to growing evidence raising serious concerns over the safety of paroxetine.

“Mind’s own research has revealed that 50 per cent of the people who contacted us to report a reaction to Seroxat had experienced feelings of wanting to self-harm or commit suicide, and 58 per cent of these people said they had not experienced these feelings before they started taking Seroxat.”

GSK said: “We will review this study carefully. However, these conclusions in no way reflect the picture that has been built up about the benefits and risks of paroxetine in adults through an extensive clinical trials programme involving 24,000 patients.”

The MHRA said that while a modest increase in suicidal thoughts and self-harm could not be ruled out for those on SSRIs, there was insufficient evidence to conclude that there is any marked difference between different SSRIs, or between SSRIs and other antidepressants.

The Norwegian group concluded: “The increased suicidal activity seen in children and adolescents on certain antidepressant drugs may well be present in adults. The restrictions in the use of paroxetine in children and adolescents conveyed by regulatory agencies lately should include usage in adults.”

Further concerns have been raised about potential suicidal side effects of a commonly used antidepressant.
The drug Seroxat (paroxetine) is already banned from use by adolescents because of an increased risk of suicidal thoughts.

In the journal BMC Medicine, University of Oslo scientists said existing studies indicated these warnings should be extended to adults.

GlaxoSmithKline, which makes the drug, said it had helped millions.

“By ignoring what mental health service users themselves have said about the medication and its effects, the drugs regulators may well have caused lives to be lost “

Sophie Corlett, Mind

Paroxetine is one in a class of drugs known as Selective Serotonin Re-uptake Inhibitors (SSRIs).

In 2003, around 19 million prescriptions for SSRIs were handed out in England for the treatment of depression and anxiety.

Concerns over suicidal side effects for those taking paroxetine were first raised by the BBC’s Panorama programme in 2002.

Last year the Medicines and Healthcare products Regulatory Agency’s (MHRA) Committee on Safety of Medicines concluded that a modest increase in the risk of suicidal thoughts and self-harm for SSRIs could not be ruled out, but the benefits for adults outweighed the risks.

Safety review

The Norwegian researchers, whose study was triggered by a journalist from the Norwegian Broadcasting Corporation working on a medical information programme, analysed the results of 16 trials involving the drug.

The studies were presented to drug regulatory agencies in 1989, prior to the drug being licensed for use by doctors in the early 1990s.

In each, patients had either been given paroxetine or a placebo (dummy pill).

The researchers carried out a statistical analysis of all the results, taking into account the length of time patients were on the drugs.

The studies included 916 patients on paroxetine and 550 patients on placebo.

There were no actual suicides in any of the studies. However, there were seven suicide attempts in the group on paroxetine, and only one in the placebo group.

Writing in BMC Medicine, the team led by Dr Ivar Aursnes, said: “Patients and doctors should be warned that the increased suicidal activity observed in children and adolescents taking certain antidepressant drugs may well be present also in adults.

“We also conclude that the recommendation of restrictions in the use of paroxetine in children and adolescents conveyed by regulatory agencies lately should include usage in adults.”

‘Confirmation’

A spokesman for GlaxoSmithKline: “We take the safety of all our medicines extremely seriously and will, of course, review this study carefully when it becomes available.”

He added: “At this stage, it’s not clear what method the researchers have used to arrive at these numbers or which clinical trials they have selected.

“However, we can say that these conclusions in no way reflect the picture that has been built up about the benefits and risks of paroxetine in adults through an extensive clinical trials programme involving 24,000 patients or through the use of this medicine in tens of millions of people around the world.”

An MHRA spokeswoman said it kept the safety of all SSRIs under close review and all new evidence was carefully reviewed and considered to see if new advice was needed.

Sophie Corlett, director of policy at the mental health charity Mind, said: “This study would seem to be an extremely worrying addition to growing evidence raising serious concerns over the safety of paroxetine.

“It confirms what Mind service users have long been telling us anecdotally.

“By ignoring what mental health service users themselves have said about the medication and its effects, the drugs regulators may well have caused lives to be lost.”

Margaret Edwards, of the mental health charity Sane, said: “Seventy per cent of those being treated with the new anti-depressants respond well, and the risks of suicide from untreated depression must be borne in mind in balancing the risks and benefits.”

Alasdair Breckenridge : “We must not get hung up on safety but instead must focus on risk-benefit”

When asked by Panorama whether GSK had acted promptly in getting the information about Seroxat’s use in children to the regulator, the MHRA’s chairman, Sir Alasdair Breckenridge, says: “This is a matter which we are investigating at the present time.

______________________________In a letter to Professor Sir Alistair Breckenridge in January, Dr John Patterson, the ABPI president, wrote: “We remain concerned at the lack of representation of the pharmaceutical industry at board level within the MHRA … As the only regulatory agency that is fully industry-funded, we believe it is essential that we have a say on a variety of issues, not least financial matters relating to fees and service levels.”

I would be obliged if you would bring our concerns to the government
regarding the MHRA, and in particular the recommendation that they should
not be as close to the pharmaceutical industry. Please do also ask the
government to explain why they continue to allow the MHRA to be funded by
industry rather than from general taxation. Clearly by allowing the MHRA to be
funded 100% by the pharmaceutical industry the government have allowed the
system of drug regulation to become corrupt!

Please read the following excerpt from a transcript of the Health Select
Committee Investigation of the Pharmaceutical Industry Influence where Dr
Ian Hudson Director of Licensing for the MHRA had been called to give
evidence but failed to appear:

Q783: John Austin – I also note that we do not have Dr Ian Hudson with us
this morning, although he was listed as one of the witnesses. Is there any
reason why not?

Professor Sir Alasdair Breckenridge: Yes, Dr Hudson is one of our delegates at
the CHMP, the Committee on Human Medical Products at the EMEA and he is
there today. He is fulfilling a different role for the agency down there

The Infamous Shell Murder Trial in which Paxil was found to blame as the cause for murder :

Glaxo’s representative in court, Ian Hudson, who now works for the Medicines Control Agency in the UK, argued that the occasional suicide or killing by somebody on Paxil is not sufficient evidence that there is a problem with the drug, considering the millions who take it.

The chief executive of Mind, the mental health charity, last night resigned from a high profile review of modern antidepressant drugs, accusing the British medicines regulatory body of negligence.
Richard Brook had a unique position as a lay member of the expert working group on the class of antidepressants which includes Seroxat and Prozac.

His resignation came in protest at what he considered a cover-up by the regulators, after months of pressure on him not to reveal the review’s findings that Seroxat has for years been prescribed by doctors in an unsafe dose and that the regulators had the evidence in their possession for more than 10 years.

Mr Brook’s resignation sheds a rare light on the workings of the secretive drug regulation agency and its advisers, and will heighten public concern over their relationships with the pharmaceutical manufacturers.

___________________________________Dr Ian Hudson is a physician who has practiced as a paediatrician for a number of years. He was formerly a research fellow at the University of Glasgow. He joined SmithKline Beecham in 1989 where he held various appointments in clinical research and development. He joined the MCA (Medicines Control Agency) in January 2001 as Director of the Licensing Division. He is the CHMP (Committee for Human Medicinal Products) delegate for the UK.

________________________________________________________
So, on Monday 29 January, Panorama promises to reveal the secret trail of internal emails which show how GSK manipulated the results of Seroxat trials in children for its own commercial gain.

The documents also reveal how the company continued to deny safety problems with the drug despite three investigations by Panorama reporter Shelley Jofre.

Almost a year ago there was another leak of secret data, this time from Dr Peter Breggin.

Each and every time more damning information becomes public, we are asked to believe that Ian Hudson did not have full knowledge of ALL the trials and data that appertained to Seroxat. Hudson was Glaxo’s Worldwide Director of Safety and had, in his own words, “a significant involvement in Paroxetine” (Seroxat).

What adds insult to injury is that this is the same Ian Hudson who now heads up the drug licensing operations of the UK regulator, the MHRA.

This is also the same Ian Hudson who decided not to appear to be questioned by the House of Commons Health Select Committee – although several senior figures from the Medicines and Healthcare Products Regulatory Agency attended the session, the committee said that it would also have liked to have heard evidence from Ian Hudson. MPs wanted to question Dr Hudson about the company’s drug paroxetine (marketed as Seroxat in Britain and as Paxil in the United States).They were particularly interested in evidence concerning the safety and efficacy of the drug in people under the age of 18.

And so we come back to the subject of the new Panorama programme which shows how GSK manipulated the results of Seroxat trials in children for its own commercial gain…

I’d like someone to ask Dr Ian Hudson where he was and what he was doing when all this was going on at Glaxo – when he had “significant involvement in Paroxetine” (Seroxat) and he was Glaxo’s Worldwide Director of Safety.

Around the time of 1998, when GSK were pushing Seroxat for other “disorders” in their bid to steal the crown off Prozac , there was some other interesting stuff going on …
Mostly concerning a pediatric (child ) study , ‘The Infamous Study 329’ ..
Up until 1998 , Seroxat was not licenced for use in children (under 18’s ) , although it was at a doctors discretion and it could be prescribed “off label” to this age group…( and it often was)
But Glaxo desperately wanted to prove that Seroxat worked in this age group (Efficacy) , if they could get a licence to treat childhood disorders with Seroxat , it would increase sales. Their profits were already massive from Seroxat ,( over a billion by 1998 ) but GSK wanted to dominate the market and they stopped at nothing in their pursuit to make Seroxat/Paxil the number one psychotropic drug worldwide.
The only problem was , they were finding it difficult to prove that Seroxat worked for kids, in fact their studies were proving placebos ( sugar pills) to be more effective than Seroxat in under-18’s …
And most disturbing of all, there were indications from Glaxo’s own trials that Seroxat increased the risk of suicide and hostility in Under 18’s, but GSK carried on regardless…

These are excerpts from the Study 329 correspondence ( they were released to the public last year, before that, they were protected under a court order )

RE: PAXll ADOLESCENT DEPRESSION PAPERDear Jim:
I am pleased to enclose a small supply of reprints of the paroxetine-imipramine
adolescent depression paper that was recently pub I ished in Journal of the American
Academy of Child and Adolescent Psychiatry. GSK funded the purchase of the
reprints. A total of 300 went to Marty Keller, who is corresponding author on the
paper, and the balance is being sent to Zach Hawkins for distribution to the
Neuroscience sales force. Samples are also being sent to Rocco and Neil.The paper looks excellent and demonstrates the commitment of GSK to the field of
psychiatry. Thank you for your support.
Sincerely,
~
Sally K. Laden, MS
Associate Editorial Director

February 6, 2001
Martin B. Keller, MD
Department of Psychiatry and Human Behavior
Brown University School of Medicine
345 Blackstone Blvd
Providence, RI 02906
Dear Dr Keller,We are pleased to enclose all of the materials you will need to resubmit your manuscript
“Efficacy of Paroxetine in the Treatment of Adolescent Major Depression: A
Randomized, Controlled Trial” to the Journal of the American Academy of Child and
Adolescent Psychiatry.
Enclosed in this package are the following items:•

Two copies of the revised paper with changes highlighted

(submit 1 to the
journal. keep 1 for your files),
• Four copies of the revised paper without the highlighting (submit 3 to the
journal, keep 1 for your files)

On behalf of Sally Laden, it has been a pleasure working with you on this project.
Please keep us apprised of the status of this paper at the journal. Thank you and please
do not hesitate to contact us if you have any questions or need additional assistance.

This “cutting-edge,” landmark study is the first to compare
efficacy of an SSRI and a TCA with placebo in the treatmen1 of
major,depression in adolescents. Paxil demonstrates
REMARKABLE Efficacy and Safety in the treatment of
adolescent depression.

In conclusion, the findings of this study provide evidence of the
efficacy and safety of Paxil in the treatment of adolescent
depression. Here’s another example of GlaxoSmithKline’ s
commitment to Psychiatry by bringing forth “cutting l~dge”
scientific data. Paxil is truly a REMARKABLE product that
continues to demonstrate efftcacy, even in this understudied
population.

________________________________________________________

So…
GSK finally got what they wanted, an academic interpretation of a clinical trial advocating the use of Seroxat in children…

Only problem was…

Study 329 didn’t actually prove anything …

It was purely GSK marketing gloss…

On the other hand study 377, did prove something…
It proved that Seroxat was no more effective than a sugar pill for the treatment of adolescent/child depression …

The two drug trials were known within SmithKline Beecham as Study 329 and Study 377.

Study 329 suggested that the company’s popular drug Paxil might help depressed adolescents. Study 377, completed not long afterward, indicated that Paxil provided no more benefit than a sugar pill in treating depressed young people.

But only the favorable study was widely publicized by Paxil’s maker. The company chose not to discuss publicly the trial with negative results, and those findings came to light only when an outside researcher on the study team decided to disclose them at a medical conference.

Federal regulators in this country are now scrambling to reassess the effectiveness and safety of antidepressants like Paxil, after British regulators touched off a controversy last year by asking drug companies for unpublished data from antidepressant trials. That data suggested that several antidepressants, including Paxil, might give rise to suicidal thoughts in some young users – a potential problem not revealed in any published studies.

Yesterday, the New York State attorney general, Eliot Spitzer, entered the fray by taking the unusual step of suing Paxil’s maker, which is now GlaxoSmithKline. Mr. Spitzer’s suit accuses the company of consumer fraud for not disclosing all of its Paxil data.

Officials of GlaxoSmithKline defend their record, saying they provided all the results of their Paxil clinical trials to the Food and Drug Administration, as required by law. But the stories of Study 329 and Study 377 provide a window into a far broader issue – the fact that the results of many human clinical trials of drugs are often never widely publicized and that, in some cases, doctors may never learn that the trials were even conducted.

These days, most drug trials are sponsored by pharmaceutical companies. And for more than a decade, a growing number of medical experts have been urging drug makers to release more trial data and to create uniform means of disclosing results through central registries, so that policy makers and doctors can easily learn the results. Those advocates argue that such central databases are necessary because drug companies, as well as medical journals and researchers, tend to spotlight only trials that show positive results

The fates of Study 329 and Study 377 appear to underscore that point. Both tests were conducted during the mid-1990’s at various hospitals and medical centers – Study 329 at facilities in the United States and Study 377 at test centers outside of this country, including Canada, Mexico, Europe, South Africa and the United Arab Emirates.

Study 329, with its potentially positive findings for Paxil, was completed first. Its results were presented beginning in 1998 at several meetings of medical professionals. Meanwhile, a report of the trial, which was led by Dr. Martin B. Keller, a department chairman at Brown University Medical School, was submitted to a medical journal for publication, a process that subjects a study to peer review by scientists not involved in the trial.

Dr. Keller declined to be interviewed for this article. But Dr. Neil Ryan, a professor at the University of Pittsburgh, who was also involved, said he believed that the study was rejected by some journals before The Journal of the Academy of Child and Adolescent Psychiatry accepted it for publication in 2001.

In the case of Study 377, the one with negative findings, there were no press releases or publications. And without the action of Dr. Milin and a Canadian colleague, Dr. Jovan Simeon, the study’s findings might have been seen only by regulators and a few researchers.

The writer of “clinical psychiatry a closer look” wrote a poignant artice about the the Study 329 shambles… Here are some excerpts …

I will focus on Dr. Martin Keller and some seriously poor science in this post. Panorama did an excellent job of profiling Keller’s role in helping to promote paroxetine (known as Paxil in the USA and Seroxat in the UK). Note this is a lengthy post and that the bold section headings should help you find your way.

Who is Martin Keller? He is chair of psychiatry at Brown University. According to his curriculum vita, he has over 300 scientific publications. People take his opinions seriously. He is what is known as a key opinion leader or thought leader in academia and by the drug industry. What does that mean? Well, on videotape (see the Panorama episode from 1-29-07), Keller said:

You’re respected for being an honorable person and therefore when you give an opinion about something, people tend to listen and say – These individuals gave their opinions; it’s worth considering.
Keller and Study 329: GlaxoSmithKline conducted a study, numbered 329, in which it examined the efficacy and safety of paroxetine versus placebo in the treatment of adolescent depression. Keller was the lead author on the article (J American Academy of Child and Adolescent Psychiatry, 2001, 762-772) which appeared regarding the results of this study.

Text of Article vs. the Actual Data: We’re going to now examine what the text of the article said versus what the data from the study said.

Article: Paroxetine is generally well-tolerated and effective for major depression in adolescents (p. 762).

Data on effectiveness: On the primary outcome variables (Hamilton Rating Scale for Depression [HAM-D] mean change and HAM-D final score What exactly were emotional lability and hostility?To quote James McCafferty, a GSK employee who helped work on Study 329, “the term emotional lability was catch all term for ‘suicidal ideation and gestures’. The hostility term captures behavioral problems, most related to parental and school confrontations.” According to Dr. David Healy, who certainly has much inside knowledge of raw data and company documents (background here), hostility counted for “homicidal acts, homicidal ideation and aggressive events.”

Suicidality is now lability and overt aggression is now hostility. Sounds much nicer that way.

Conveniently defining depression: On page 770 of the study report, the authors opined that “…our study demonstrates that treatment with paroxetine results in clinically relevant improvement in depression scores.” The only measures that showed an advantage for paroxetine were either based on some arbitrary cutoff (and the researchers could of course opt for whatever cutoff yielded the results they wanted) or were not actually valid measures of depression. The only measures that were significant were either a global measure of improvement, which paints an optimistic view of treatment outcome, or were cherry-picked single items from longer questionnaires.

Also, think about the following for a moment. A single question on any questionnaire or interview is obviously not going to broadly cover symptoms of depression. A single question cannot cover the many facets of depression. Implying that a single question on an interview which shows an advantage for paroxetine shows that paroxetine is superior in treating depression is utterly invalid. Such logic is akin to finding that a patient with the flu reports coughing less often on a medication compared to placebo, so the medication is then declared superior to placebo for managing flu despite the medication not working better on any of the many other symptoms that comprise influenza.Whitewashing safety data: It gets even more bizarre. Remember those 10 people who had serious adverse psychiatric events while taking paroxetine? Well, the researchers concluded that none of the adverse psychiatric events were caused by paroxetine. Interestingly, the one person who became “labile” on placebo – that event was attributed to placebo. In this magical study, a drug cannot make you suicidal but a placebo can.In a later document, Keller and colleagues said that “acute psychosocial stressors, medication noncompliance, and/or untreated comorbid disorders were judged by the investigators to account for the adverse effects in all 10 patients.” This sounds to me as if the investigators had concluded beforehand that paroxetine is incapable of making participants worse and they just had to drum up some other explanation as to why these serious events were occurring. David Healy has also discussed this fallacious assumption that drugs cannot cause harm.

Did Keller Know the Study Data? I’ll paraphrase briefly from Panorama, which had a video of Keller discussing the study and his role in examining and analyzing its data. He said he had reviewed data analytic tables, but then he mentioned soon after that on some printouts there were “item numbers and variable numbers and they don’t even have words on them – I tend not to look at those. I do better with words than symbols. [emphasis mine].”

Ghosted: According to Panorama (and documents I’ve obtained), the paper was written by a ghostwriter.Keller’s response to the ghostwriter after he saw the paper? “You did a superb job with this. Thank you very much. It is excellent. Enclosed are some rather minor changes from me, Neal, and Mike. [emphasis mine].” And let’s remember that Keller apparently did not wish to bother with looking at numbers. It would also appear that he did not want to bother much with the words based upon those numbers.

Third Party Technique: This is a tried and true trick – get several leading academics to stamp their names on a study manuscript and suddenly it appears like the study was closely supervised in every aspect, from data collection to data analysis, to study writeup, by independent academics. Thus, it is not GlaxoSmithKline telling you that their product is great, it is “independent researchers” from such bastions of academia as Brown University, the University of Pittsburgh, and University of Texas Southwester Medical Center and the University of Texas Medical Branch at Galveston which are stamping approval of the product. More on this in future posts.

Keller’s Background… It is relatively well-known that Keller makes much money from his consulting and research arrangements with drug companies. In fact, several years ago, it was documented that Keller pulled in over $500,000 in a single year through these lucrative deals. When looking at how he stuck his name on a study he did not write, endorsing conclusions that were clearly far from the actual study data, can one seriously believe that Keller operated as an independent researcher? Can you believe that this is an isolated incident?

See, for example, Keller’s involvement in a study examining the effects of Risperdal (risperidone) for the treatment of depression. This study was presented a number of times, and he never appeared as an author of any of the presentations. Yet when the study was published, his name appeared as an author. The real kicker was that he allegedly helped to design the study, according to the published article. If he had played a major role in the study, he would have been acknowledged earlier (via being listed as a presentation author), so he apparently helped design the study after it was completed, which is obviously a major feat! The whole story is here. Why put his name on the paper? So that readers would believe more strongly in the study due to his big name status.

In addition, Keller wrote about how Effexor reduces episodes of depression in the long-term though he clearly misinterpreted the study’s findings. To be fair, many other researchers have made the same mistake in believing that SSRI’s reduce depression. To quote an earlier post:

In other words, because SSRIs and similar drugs (e.g., Effexor) have withdrawal symptoms that sometimes lead to depression, it looks like they are effective in preventing depression because people often get worse shortly after stopping their medication. The drug companies (Wyeth, in the case of Effexor) would like you to believe that this means antidepressants protect you from re-experiencing depression once you get better, that they are a good long-term treatment. A more accurate statement is that antidepressants protect you from their own substantial withdrawal symptoms until you stop taking them.
Again, Keller is way off from the study data.

Keller on Camera: Keller’s response to being asked about the increased suicidality among participants taking paroxetine in Study 329 was interesting:

None of these attempts led to suicide and very few of them led to hospitalization.

Well then I suppose a huge increase in suicidal thoughts and gestures is okay, then? This is the commentary of an “opinion leader” – if statements such as the above shape opinions among practicing psychiatrists, then we really are in trouble.
Next: Well, consider this post just the start regarding Paxil/Seroxat. The way the data were pimped by GSK merits more discussion as does more discussion of allegedly detached academics and their role in this debacle.
___________________________________________________________________________________________

Like this:

So far , Through the links I have provided on this blog, we can see where Seroxat came from, How GSK unscrupulously hoodwinked it passed the regulators (MHRA and FDA) and obtained a market to promote what was originally classified as a “hypnotic” chemical as an “antidepressant” treatment… Seroxat was then released to an unsuspecting and trusting public in 1991 , I call this The first wave , because it seems that from this period until 1998 , GSK were testing the waters with Seroxat , gathering data on how it would perform …How much could they get away with?

But it was in 1998, (when Seroxat was relicenced )that GSK Stepped up a gear, GSK went on a marketing Blitz … A triumph of Marketing over Science.. With the help of devious sales tactics, In 1998 , GSK turned Seroxat into a blockbuster…

Here is how they went about it :

Seroxat : For Shyness

New pill to beat shyness
Sunday Mirror, Oct 4, 1998

A PILL to combat shyness is being launched this week and will be available on the NHS.

The drug, which could relieve the symptoms of up to three million chronically- shy people in Britain, is reported to improve the condition within a week in some cases.

Seroxat, which was originally licensed to treat depression, has now been given the go-ahead to fight shyness and “social phobias”.

The drug works by increasing the level of seratonin in the brain, and could cost the NHS up to pounds 700 million a year if all the country’s shy people took it.

Thursday, 23 July, 1998, 08:56 GMT 09:56 UK
Shy? Try taking a pill

Social wallflowers could be transformed into outgoing party animals with the help of a new drug.SmithKline Beecham claims its anti-depression drug Seroxat, launched in the UK in 1992, has been shown in tests to cure ‘social phobia’.

It has applied to the US Food and Drug Administration for a licence to use the drug, now prescribed for panic attacks, for people diagnosed as having acute shyness.

The media has climbed onto the Seroxat bandwagon, hailing it as the big new thing in social drugs after anti-impotence pill Viagra.

They say Seroxat will help shy people get to the point where they might need Viagra.

The downside is that Seroxat can reduce sexual drive and function.

Serotonin

The drug boosts the level of serotonin in the brain – the hormone which controls people’s moods.

It is already a major success at treating depression and its sales have risen by 23% in the last year.

It now accounts for one quarter of US anti-depressant drug sales and it was the fastest selling anti-depressant drug in the UK in the mid-1990s. In 1996, UK sales grew by 50%.

But if it gets approval to be used to treat acute shyness, sales are likely to soar.

A spokesman for SmithKline Beecham said shyness was ‘ a serious condition’ and that only those who had acute problems would be prescribed the drug by doctors.

“It would be used for the sort of people who would have to run out of a crowded room. The underlying problem is usually extreme anxiety,” he said.

PHILADELPHIA, PA — Seroxat/Paxil (paroxetine HCl) has been approved for the treatment of social anxiety disorder in the United Kingdom, SmithKline Beecham announced today. It is the first selective serotonin re-uptake inhibitor (SSRI) to be approved for this severely debilitating and little known anxiety disorder. Seroxat/Paxil is currently under review for this indication throughout

Pill to melt shyness

Most people call it extreme shyness. According to some experts, up to eleven per cent of people in Ireland suffer from it. They prefer to call extreme shyness “social phobia” and they say that people who suffer from it experience unimaginable torment and isolation.

Now doctors believe Seroxat, a pill to counteract depression, can also help these social phobics or people who are, literally, painfully shy.

Now, new research in Britain which reveals that the anti-depressant drug Seroxat successfully treats the condition has brought the plight of social phobics into the public mind for the first time.

On 9th January 1998, in the face of mounting adverse reports from users and GPs, Seroxat was re-licensed for a wider range of symptoms including depression accompanied with anxiety, obsessive compulsive disorder and panic disorder. Off label prescription included pre-menstrual tension and irritable bowel syndrome. This wider remit increased sales dramatically and for the first time people who had never been depressed or suicidal were being prescribed Seroxat. Unbeknown to them, they were exposed to the additional risk of dependency syndrome and a raised risk of suicide. No longer could depression, suicidal thoughts and acts suffered by these people be attributed to a relapse of their depressive illness.

Revealed: secret plan to push’happy’ pills

Jamie Doward and Robin McKie
Sunday November 7, 2004
The Observer

Britain’s largest drug company drew up a secret plan to double sales of the controversial anti-depressant Seroxat by marketing it as a cure for a raft of less serious mental conditions,

The contents of the 250-page document have alarmed health campaigners who accuse the firm, GlaxoSmithKline (GSK), of putting profit before the therapeutic needs of patients by attempting to broaden the market for the drug which has been linked to a spate of suicides.

The internal report carries a section which outlines how GSK planned to double sales of ‘selective serotonin reuptake inhibitors (SSRI)’ – the industry term for anti-depressants – by winning the marketing war against Seroxat’s chief rival, Prozac, manufacured by Eli Lilly.

Written in 1998 and subsequently updated in following years, the section is entitled: ‘Towards the second billion – all SSRIs are not the same’ and discusses strategies to see off the threat posed by Prozac.

The document outlined how GSK intended to market Seroxat for a range of conditions other than clinical depression. Chief among these was a condition the company identified as social anxiety disorder, although other forms of anxiety were also discussed internally.

‘What this document makes clear is that a number of different forms of anxiety were being targeted in a systematic way. The thrust was to move sales beyond the $1 billion to $2 billion mark by pushing it to people who were not clinically depressed,’ said Professor David Healy, a psycho-pharmacologist at Cardiff University, who has given evidence to the House of Commons Health Select Committee.

Richard Brook, chief executive of Mind, the mental health charity which submitted the document to the committee, told the MPs it was ‘all about developing new conditions for that drug and demolishing the arguments of other competitors about why their drug was not any good’.

In addition the document shows GSK made a great virtue of the fact that Seroxat had a relatively short ‘half-life’ compared with Prozac, an argument which has subsequently proven deeply controversial.

A half-life is the scientific term for how long it takes for the concentration of a drug to drop by 50 per cent in a patient’s bloodstream. The company suggested Seroxat’s short half-life meant patients could come on and off the drug easily, compared with those on Prozac, even to the extent that they could take ‘treatment holidays’. ‘There was an argument that a short half life was really good news,’ Brook said.

But five years later, Seroxat has withdrawal issues. It’s the short half life that causes the problems. The substances get into the body so quickly it causes some sort of dependency reaction. So one of the things the company was saying was a benefit was actually a problem.’

In its submission to the parliamentary committee Mind said the original trial data submitted to the UK regulators by GSK showed the claim was at best ‘naive and at worst seriously mislead ing’. It added that ‘the Seroxat file is highly illustrative of using marketing information as facts’.

Concerns about the addictive properties of Seroxat saw the government ban its prescription to people under the age of 18 last year. This followed a review which found children taking it were more likely to self-harm or commit suicide.

A spokesman for GSK said Seroxat could be marketed at new conditions only after stringent testing. ‘Medical authorities around the world have required that GSK study each condition separately in order to prove benefit in each condition specifically.’